I like Gris Gris, his first album.
Allmusic says:
The most exploratory and psychedelic outing of Dr. John's career, a one-of-a-kind fusion of New Orleans Mardi Gras R&B and voodoo mysticism. Great rasping, bluesy vocals, soulful backup singers, and eerie melodies on flute, sax, and clarinet, as well as odd Middle Eastern-like chanting and mandolin runs. It's got the setting of a strange religious ritual, but the mood is far more joyous than solemn